Defining GM-CSF- and Macrophage-CSF Dependent Macrophage Responses by In Vitro Models

Defining GM-CSF- and Macrophage-CSF Dependent Macrophage Responses by In Vitro Models
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DOI:
10.4049/jimmunol.1103426
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发表时间:
2012-06-01
影响因子:
4.4
通讯作者:
Hamilton, John A.
Hamilton, John A.
中科院分区:
医学2区
文献类型:
--
作者:
Lacey, Derek C.;Achuthan, Adrian;Hamilton, John A.

文献摘要

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GM-CSF和M-CSF (CSF-1)在巨噬细胞谱系群体中诱导不同的表型变化。通过比较不同人类和小鼠巨噬细胞谱系群体对这些csf的单独或联合反应,评估了这些差异的性质、程度和普遍性。将GM-CSF或M-CSF衍生自人单核细胞的巨噬细胞各自基因表达谱的差异与每种CSF衍生自小鼠骨髓细胞的巨噬细胞各自基因表达谱的差异进行比较。这些csf调控的基因中只有17%在整个物种中是共同的。相对基因表达的特定变化是否由CSF的直接作用引起,内源性介质(如I型IFN、IL-10和激活素a)可能会混淆。在用CSF处理的人单核细胞中,细胞因子基因表达的时间依赖性差异被注意到;在该系统中,GM-CSF诱导ifn调节因子4 (IRF4)的表达比IRF5更显著,而M-CSF诱导IRF5而不诱导IRF4。在这两种csf存在的情况下,在基因表达水平上观察到一些“竞争”的证据。当从一个特定的体外系统中得出关于GM-CSF和M-CSF在巨噬细胞谱系生物学中的作用的明确结论时,需要谨慎。中华免疫学杂志,2012,18(8):5752-5765。
GM-CSF and M-CSF (CSF-1) induce different phenotypic changes in macrophage lineage populations. The nature, extent, and generality of these differences were assessed by comparing the responses to these CSFs, either alone or in combination, in various human and murine macrophage lineage populations. The differences between the respective global gene expression profiles of macrophages, derived from human monocytes by GM-CSF or M-CSF, were compared with the differences between the respective profiles for macrophages, derived from murine bone marrow cells by each CSF. Only 17% of genes regulated differently by these CSFs were common across the species. Whether a particular change in relative gene expression is by direct action of a CSF can be confounded by endogenous mediators, such as type I IFN, IL-10, and activin A. Time-dependent differences in cytokine gene expression were noted in human monocytes treated with the CSFs; in this system, GM-CSF induced a more dramatic expression of IFN-regulated factor 4 (IRF4) than of IRF5, whereas M-CSF induced IRF5 but not IRF4. In the presence of both CSFs, some evidence of "competition" at the level of gene expression was observed. Care needs to be exercised when drawing definitive conclusions from a particular in vitro system about the roles of GM-CSF and M-CSF in macrophage lineage biology. The Journal of Immunology, 2012, 188: 5752-5765.